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The cerebellum plays an important role in cognitive and social functioning. Childhood damage in the cerebellum increases the risk of autism spectrum disorder. Cerebellar inflammation induces social avoidance in mice. Oxytocin regulates social relationship and expression pattern of the oxytocin receptor in the brain is related to social behaviors. However, the expression patterns of the oxytocin receptor in the cerebellum remain controversial. Here, we report that the expression patterns of the oxytocin receptor in the cerebellum are highly variable among knock-in transgenic lines. We used Oxtr-Cre knock-in mice combined with a fluorescent reporter line and found that oxytocin receptor expression in Bergmann glia was more variable than that in Purkinje cells. We found that physical damage with inflammation induced the selective upregulation of the oxytocin receptor in Bergmann glia. Our findings indicate high variability in oxytocin receptor expression in the cerebellum and suggest that the oxytocin receptor can affect neural processing in pathological conditions, such as inflammation.
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Cerebelo , Inflamación , Ratones Transgénicos , Neuroglía , Receptores de Oxitocina , Regulación hacia Arriba , Receptores de Oxitocina/metabolismo , Receptores de Oxitocina/genética , Animales , Neuroglía/metabolismo , Neuroglía/patología , Cerebelo/patología , Cerebelo/metabolismo , Inflamación/patología , Inflamación/metabolismo , Ratones Endogámicos C57BL , Ratones , Masculino , Células de Purkinje/metabolismo , Células de Purkinje/patologíaRESUMEN
Introduction: Within the realm of chemogenetics, a particular form of agonists targeting designer receptors exclusively activated by designer drugs (DREADDs) has emerged. Deschloroclozapine (DCZ), a recently introduced DREADDs agonist, demonstrates remarkable potency in activating targeted neurons at a lower dosage compared to clozapine-N-oxide (CNO). Methods: We conducted a comparative analysis of the effects of subcutaneously administered CNO (1 mg/kg) and DCZ (0.1 mg/kg) in our transgenic rats expressing hM3Dq and mCherry exclusively in oxytocin (OXT) neurons. Results and Discussion: Notably, DCZ exhibited a swift and robust elevation of serum OXT, surpassing the effects of CNO, with a significant increase in the area under the curve (AUC) up to 3 hours post-administration. Comprehensive assessment of brain neuronal activity, using Fos as an indicator, revealed comparable effects between CNO and DCZ. Additionally, in a neuropathic pain model, both CNO and DCZ increased the mechanical nociceptive and thermal thresholds; however, the DCZ-treated group exhibited a significantly accelerated onset of the effects, aligning harmoniously with the observed alterations in serum OXT concentration following DCZ administration. These findings emphasize the remarkable efficacy of DCZ in rats, suggesting its equivalent or potentially superior performance to CNO at considerably lower dosages, thus positioning it as a promising contender among DREADDs agonists.
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Resilience is a term that describes the capacity of coping with and recovering from stress and adversity. In terms of the concept of allostasis, resilience is the ability to appropriately regulate allostasis, efficiently terminate the allostatic response, prevent the occurrence of allostatic load/overload or restore homeostasis. Recently, it has been shown that oxytocin may be involved in this series of stress adaptation systems. We aim to discuss the changes in oxytocin neuron activation, oxytocin release and its actions of stress adaptation in response to internal and external environmental changes, and the regulation of resilience by oxytocin.
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Alostasis , Humanos , Alostasis/fisiología , Oxitocina , Estrés Fisiológico/fisiología , Adaptación Psicológica , Homeostasis/fisiología , Estrés PsicológicoRESUMEN
Fibromyalgia (FM) is a syndrome characterized by chronic pain with depression as a frequent comorbidity. However, efficient management of the pain and depressive symptoms of FM is lacking. Given that endogenous oxytocin (OXT) contributes to the regulation of pain and depressive disorders, herein, we investigated the role of OXT in an experimental reserpine-induced FM model. In FM model, OXT-monomeric red fluorescent protein 1 (OXT-mRFP1) transgenic rats exhibited increased depressive behavior and sensitivity in a mechanical nociceptive test, suggesting reduced pain tolerance. Additionally, the development of the FM-like phenotype in OXT-mRFP1 FM model rats was accompanied by a significant reduction in OXT mRNA expression in the magnocellular neurons of the paraventricular nucleus. OXT-mRFP1 FM model rats also had significantly fewer tryptophan hydroxylase (TPH)- and tyrosine hydroxylase (TH)-immunoreactive (ir) neurons as well as reduced serotonin and norepinephrine levels in the dorsal raphe and locus coeruleus. To investigate the effects of stimulating the endogenous OXT pathway, rats expressing OXT-human muscarinic acetylcholine receptor (hM3Dq)-mCherry designer receptors exclusively activated by designer drugs (DREADDs) were also assessed in the FM model. Treatment of these rats with clozapine-N-oxide (CNO), an hM3Dq-activating drug, significantly improved characteristic FM model-induced pathophysiological pain, but did not alter depressive-like behavior. The chemogenetically induced effects were reversed by pre-treatment with an OXT receptor antagonist, confirming the specificity of action via the OXT pathway. These results indicate that endogenous OXT may have analgesic effects in FM, and could be a potential target for effective pain management strategies for this disorder.
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Fibromialgia , Oxitocina , Ratas , Humanos , Animales , Oxitocina/farmacología , Oxitocina/metabolismo , Reserpina/farmacología , Reserpina/metabolismo , Fibromialgia/inducido químicamente , Fibromialgia/metabolismo , Proteínas Luminiscentes/genética , Dolor/metabolismo , Ratas Transgénicas , Neuronas/metabolismo , Receptores de Oxitocina/metabolismoRESUMEN
Whether commonly used experimental animals show aversion toward inequality of social rewards, as humans do remains unknown. We examined whether rats emitted the 22-kHz distress calls under social reward inequality. Rats showed affiliative behavior for a specific human who repeatedly stroked and tickled them. When experimenter stroked another rat in front of them and during social isolation, these rats emitted novel calls with acoustic characteristics different from those of calls emitted under physical stress, namely air-puff. Under inequality conditions, rats emitted calls with higher frequency (â¼31 kHz) and shorter duration (<0.5 s) than those emitted when receiving air-puff. However, with an affiliative human in front of them, the number of novel calls was lower and rats emitted 50-kHz calls, indicative of the appetitive state. These results indicate that rats distinguish between conditions of social reward inequality and the presence of an experimenter, and emit novel 31-kHz calls.
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The CRISPR-Cas9 method for generation of knock-in mutations in rodent embryos yields many F0 generation candidates that may have the designed mutations. The first task for selection of promising F0 generations is to analyze genomic DNA which likely contains a mixture of designed and unexpected mutations. In our study, while generating Prlhr-Venus knock-in reporter mice, we found that genomic rearrangements near the targeted knock-in allele, tandem multicopies at a target allele locus, and mosaic genotypes for two different knock-in alleles occurred in addition to the designed knock-in mutation in the F0 generation. Conventional PCR and genomic sequencing were not able to detect mosaicism nor discriminate between the designed one-copy knock-in mutant and a multicopy-inserted mutant. However, by using a combination of Southern blotting and the next-generation sequencing-based RAISING method, these mutants were successfully detected in the F0 generation. In the F1 and F2 generations, droplet digital PCR assisted in establishing the strain, although a multicopy was falsely detected as one copy by analysis of the F0 generation. Thus, the combination of these methods allowed us to select promising F0 generations and facilitated establishment of the designed strain. We emphasize that focusing only on positive evidence of knock-in can lead to erroneous selection of undesirable strains.
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Sistemas CRISPR-Cas , Genómica , Ratones , Animales , Sistemas CRISPR-Cas/genética , Secuencia de Bases , Mutación , AlelosRESUMEN
Transgenic animals expressing fluorescent proteins are widely used to label specific cells and proteins. By using a split Cre recombinase fused with mCherry-binding nanobodies or designed ankyrin repeat proteins, we created Cre recombinase dependent on red fluorescent protein (RFP) (Cre-DOR). Functional binding units for monomeric RFPs are different from those for polymeric RFPs. We confirmed selective target RFP-dependent gene expression in the mouse cerebral cortex using stereotaxic injection of adeno-associated virus vectors. In estrogen receptor-beta (Esr2)-mRFP1 mice and gastrin-releasing peptide receptor (Grpr)-mRFP1 rats, we confirmed that Cre-DOR can be used for selective tracing of the neural projection from RFP-expressing specific neurons. Cellular localization of RFPs affects recombination efficiency of Cre-DOR, and light and chemical-induced nuclear translocation of an RFP-fused protein can modulate Cre-DOR efficiency. Our results provide a method for manipulating gene expression in specific cells expressing RFPs and expand the repertory of nanobody-based genetic tools.
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Receptores de Bombesina , Anticuerpos de Dominio Único , Animales , Integrasas , Proteínas Luminiscentes , Ratones , Ratones Transgénicos , Ratas , Receptores de Estrógenos , Anticuerpos de Dominio Único/genética , Proteína Fluorescente RojaRESUMEN
Oxytocin is involved in pain transmission, although the detailed mechanism is not fully understood. Here, we generate a transgenic rat line that expresses human muscarinic acetylcholine receptors (hM3Dq) and mCherry in oxytocin neurons. We report that clozapine-N-oxide (CNO) treatment of our oxytocin-hM3Dq-mCherry rats exclusively activates oxytocin neurons within the supraoptic and paraventricular nuclei, leading to activation of neurons in the locus coeruleus (LC) and dorsal raphe nucleus (DR), and differential gene expression in GABA-ergic neurons in the L5 spinal dorsal horn. Hyperalgesia, which is robustly exacerbated in experimental pain models, is significantly attenuated after CNO injection. The analgesic effects of CNO are ablated by co-treatment with oxytocin receptor antagonist. Endogenous oxytocin also exerts anti-inflammatory effects via activation of the hypothalamus-pituitary-adrenal axis. Moreover, inhibition of mast cell degranulation is found to be involved in the response. Taken together, our results suggest that oxytocin may exert anti-nociceptive and anti-inflammatory effects via both neuronal and humoral pathways.
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Analgésicos , Antiinflamatorios , Oxitocina , Núcleo Hipotalámico Paraventricular , Analgésicos/metabolismo , Animales , Antiinflamatorios/metabolismo , Neuronas GABAérgicas/metabolismo , Oxitocina/metabolismo , Dolor/tratamiento farmacológico , Núcleo Hipotalámico Paraventricular/metabolismo , Ratas , Ratas TransgénicasRESUMEN
In humans, tear volume increases during emotional arousal. To our knowledge, no previous studies have investigated the relationship between emotional arousal and tear volume in animals. We performed the Schirmer tear test (STT) and measured tear volume in dogs before and after reunions with owners and familiar non-owners. Tear volume increased significantly during reunion with the owner, but not with a familiar non-owner. When an oxytocin solution was applied to dogs' eyes, the tear volume also increased, suggesting that oxytocin might mediate tear secretion during owner-dog reunions. Finally, human participants rated their impressions on photos of dogs with or without artificial tears and they assigned more positive scores to the photos with artificial tears. These results suggest that emotion-elicited tears can facilitate human-dog emotional connections. VIDEO ABSTRACT.
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Gotas Lubricantes para Ojos , Oxitocina , Animales , Perros , Emociones , Humanos , Oxitocina/farmacología , LágrimasRESUMEN
During obesity, tissue macrophages increase in number and become proinflammatory, thereby contributing to metabolic dysfunction. Lipoprotein lipase (LPL), which hydrolyzes triglyceride in lipoproteins, is secreted by macrophages. However, the role of macrophage-derived LPL in adipose tissue remodeling and lipoprotein metabolism is largely unknown. To clarify these issues, we crossed leptin-deficient Lepob/ob mice with mice lacking the Lpl gene in myeloid cells (Lplm-/m-) to generate Lplm-/m-;Lepob/ob mice. We found the weight of perigonadal white adipose tissue (WAT) was increased in Lplm-/m-;Lepob/ob mice compared with Lepob/ob mice due to substantial accumulation of both adipose tissue macrophages and collagen that surrounded necrotic adipocytes. In the fibrotic epidydimal WAT of Lplm-/m-;Lepob/ob mice, we observed an increase in collagen VI and high mobility group box 1, while α-smooth muscle cell actin, a marker of myofibroblasts, was almost undetectable, suggesting that the adipocytes were the major source of the collagens. Furthermore, the adipose tissue macrophages from Lplm-/m-;Lepob/ob mice showed increased expression of genes related to fibrosis and inflammation. In addition, we determined Lplm-/m-;Lepob/ob mice were more hypertriglyceridemic than Lepob/ob mice. Lplm-/m-;Lepob/ob mice also showed slower weight gain than Lepob/ob mice, which was primarily due to reduced food intake. In conclusion, we discovered that the loss of myeloid Lpl led to extensive fibrosis of perigonadal WAT and hypertriglyceridemia. In addition to illustrating an important role of macrophage LPL in regulation of circulating triglyceride levels, these data show that macrophage LPL protects against fibrosis in obese adipose tissues.
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Tejido Adiposo Blanco , Colágeno Tipo IV , Hipertrigliceridemia , Lipoproteína Lipasa , Obesidad , Actinas/metabolismo , Tejido Adiposo Blanco/patología , Animales , Colágeno Tipo IV/metabolismo , Fibrosis , Hipertrigliceridemia/genética , Hipertrigliceridemia/patología , Leptina/deficiencia , Leptina/genética , Lipoproteína Lipasa/genética , Lipoproteínas/metabolismo , Ratones , Ratones Obesos , Obesidad/genética , Obesidad/metabolismo , Obesidad/patología , Triglicéridos/sangreRESUMEN
Arginine vasopressin (AVP) is a hypothalamic neurosecretory hormone well known as an antidiuretic, and recently reported to be involved in pain modulation. The expression kinetics of AVP and its potential involvement in the descending pain modulation system (DPMS) in neuropathic pain (NP) remains unclear. We investigated AVP expression and its effects on mechanical and thermal nociceptive thresholds using a unilateral spinal nerve ligation (SNL) model. All rats with SNL developed NP. Intensities of enhanced green fluorescent protein (eGFP) in the supraoptic and paraventricular nuclei, median eminence, and posterior pituitary were significantly increased at 7 and 14 days post-SNL in AVP-eGFP rats. In situ hybridisation histochemistry revealed significantly increased AVP mRNA expression at 14 days post-SNL compared with the sham control group. The chemogenetic activation of AVP neurones significantly attenuated mechanical and thermal hyperalgesia with elevated plasma AVP concentration. These analgesic effects were suppressed by pre-administration with V1a receptor antagonist. AVP neurones increased the neuronal activity of serotonergic dorsal raphe, noradrenergic locus coeruleus, and inhibitory interneurones in the spinal dorsal horn. These results suggest that the hypothalamo-neurohypophysial system of AVP is upregulated in NP and activated endogenous AVP exerts analgesic effects via the V1a receptors. AVP neurones may activate the DPMS.
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Hiperalgesia , Neuralgia , Analgésicos , Animales , Arginina Vasopresina/metabolismo , Arginina Vasopresina/farmacología , Ratas , Regulación hacia Arriba , Vasopresinas/metabolismoRESUMEN
Arginine vasopressin (AVP) is produced in the paraventricular (PVN) and supraoptic nuclei (SON). Peripheral AVP, which is secreted from the posterior pituitary, is produced in the magnocellular division of the PVN (mPVN) and SON. In addition, AVP is produced in the parvocellular division of the PVN (pPVN), where corticotrophin-releasing factor (CRF) is synthesized. These peptides synergistically modulate the hypothalamic-pituitary-adrenal (HPA) axis. Previous studies have revealed that the HPA axis was activated by hypovolemia. However, the detailed dynamics of AVP in the pPVN under hypovolemic state has not been elucidated. Here, we evaluated the effects of hypovolemia and hyperosmolality on the hypothalamus, using AVP-enhanced green fluorescent protein (eGFP) transgenic rats. Polyethylene glycol (PEG) or 3% hypertonic saline (HTN) was intraperitoneally administered to develop hypovolemia or hyperosmolality. AVP-eGFP intensity was robustly upregulated at 3 and 6 h after intraperitoneal administration of PEG or HTN in the mPVN. While in the pPVN, eGFP intensity was significantly increased at 6 h after intraperitoneal administration of PEG with significant induction of Fos-immunoreactive (-ir) neurons. Consistently, eGFP mRNA, AVP hnRNA, and CRF mRNA in the pPVN and plasma AVP and corticosterone were significantly increased at 6 h after intraperitoneal administration of PEG. The results suggest that AVP and CRF syntheses in the pPVN were activated by hypovolemia, resulting in the activation of the HPA axis.
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Arginina Vasopresina/genética , Proteínas Fluorescentes Verdes/genética , Sistema Hipotálamo-Hipofisario/metabolismo , Hipovolemia/metabolismo , Núcleo Hipotalámico Paraventricular/metabolismo , Animales , Corticosterona/sangre , Hormona Liberadora de Corticotropina/genética , Hormona Liberadora de Corticotropina/metabolismo , Modelos Animales de Enfermedad , Genes Reporteros , Proteínas Fluorescentes Verdes/biosíntesis , Sistema Hipotálamo-Hipofisario/fisiopatología , Hipovolemia/genética , Hipovolemia/fisiopatología , Inyecciones Intraperitoneales , Masculino , Núcleo Hipotalámico Paraventricular/fisiopatología , Polietilenglicoles/administración & dosificación , Proteínas Proto-Oncogénicas c-fos/metabolismo , Ratas Transgénicas , Ratas Wistar , Solución Salina Hipertónica/administración & dosificación , Núcleo Supraóptico/metabolismo , Núcleo Supraóptico/fisiopatología , Factores de Tiempo , Regulación hacia ArribaRESUMEN
Vasopressin-synthesizing neurons are located in several brain regions, including the hypothalamic paraventricular nucleus (PVN), supraoptic nucleus (SON) and suprachiasmatic nucleus (SCN). Vasopressin has been shown to have various functions in the brain, including social recognition memory, stress responses, emotional behaviors and circadian rhythms. The precise physiological functions of vasopressin-synthesizing neurons in specific brain regions remain to be clarified. Conditional ablation of local vasopressin-synthesizing neurons may be a useful tool for investigation of the functions of vasopressin neurons in the regions. In the present study, we characterized a transgenic rat line that expresses a mutated human diphtheria toxin receptor under control of the vasopressin gene promoter. Under a condition of salt loading, which activates the vasopressin gene in the hypothalamic PVN and SON, transgenic rats were i.c.v. injected with diphtheria toxin. Intracerebroventricular administration of diphtheria toxin after salt loading depleted vasopressin-immunoreactive cells in the hypothalamic PVN and SON, but not in the SCN. The number of oxytocin-immunoreactive cells in the hypothalamus was not significantly changed. The rats that received i.c.v. diphtheria toxin after salt loading showed polydipsia and polyuria, which were rescued by peripheral administration of 1-deamino-8-d-arginine vasopressin via an osmotic mini-pump. Intrahypothalamic administration of diphtheria toxin in transgenic rats under a normal hydration condition reduced the number of vasopressin-immunoreactive neurons, but not the number of oxytocin-immunoreactive neurons. The transgenic rat model can be used for selective ablation of vasopressin-synthesizing neurons and may be useful for clarifying roles of vasopressin neurons at least in the hypothalamic PVN and SON in the rat.
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Técnicas de Transferencia de Gen , Genes Transgénicos Suicidas , Neuronas/metabolismo , Vasopresinas/metabolismo , Animales , Apoptosis/efectos de los fármacos , Apoptosis/genética , Toxina Diftérica/farmacología , Eliminación de Gen , Genes Transgénicos Suicidas/efectos de los fármacos , Factor de Crecimiento Similar a EGF de Unión a Heparina/genética , Factor de Crecimiento Similar a EGF de Unión a Heparina/metabolismo , Masculino , Neuronas/efectos de los fármacos , Núcleo Hipotalámico Paraventricular/efectos de los fármacos , Núcleo Hipotalámico Paraventricular/metabolismo , Ratas , Ratas Endogámicas Lew , Ratas Transgénicas , Núcleo Supraóptico/efectos de los fármacos , Núcleo Supraóptico/metabolismo , Vasopresinas/genéticaRESUMEN
Early-life experience influences social and emotional behaviour in adulthood. Affiliative tactile stimuli in early life facilitate the development of social and emotional behaviour, whereas early-life adverse stimuli have been shown to increase the risk of various diseases in later life. On the other hand, oxytocin has been shown to have organizational actions during early-life stages. However, the detailed mechanisms of the effects of early-life experience and oxytocin remain unclear. Here, we review the effects of affiliative tactile stimuli during the neonatal period and neonatal oxytocin treatment on the activity of the oxytocin-oxytocin receptor system and social or emotional behaviour in adulthood. Both affiliative tactile stimuli and early-life adverse stimuli in the neonatal period acutely activate the oxytocin-oxytocin receptor system in the brain but modulate social behaviour and anxiety-related behaviour apparently in an opposite direction in adulthood. Accumulating evidence suggests that affiliative tactile stimuli and exogenous application of oxytocin in early-life stages induce higher activity of the oxytocin-oxytocin receptor system in adulthood, although the effects are dependent on experimental procedures, sex, dosages and brain regions examined. On the other hand, early-life stressful stimuli appear to induce reduced activity of the oxytocin-oxytocin receptor system, possibly leading to adverse actions in adulthood. It is possible that activation of a specific oxytocin system can induce beneficial actions against early-life maltreatments and thus could be used for the treatment of developmental psychiatric disorders.
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Oxitocina , Adulto , Emociones , Humanos , Recién Nacido , Oxitocina/farmacología , Receptores de Oxitocina , Conducta SocialRESUMEN
Fibroblast growth factor 21 (FGF21) modulates energy metabolism and neuroendocrine stress responses. FGF21 synthesis is increased after environmental or metabolic challenges. Detailed roles of FGF21 in the control of behavioural disturbances under stressful conditions remain to be clarified. Here, we examined the roles of FGF21 in the control of behavioural changes after social defeat stress in male rodents. Central administration of FGF21 increased the number of tyrosine hydroxylase-positive catecholaminergic cells expressing c-Fos protein, an activity marker of neurones, in the nucleus tractus solitarius and area postrema. Double in situ hybridisation showed that some catecholaminergic neurones in the dorsal medulla oblongata expressed ß-Klotho, an essential co-receptor for FGF21, in male mice. Social defeat stress increased FGF21 concentrations in the plasma of male mice. FGF21-deficient male mice showed social avoidance in a social avoidance test with C57BL/6J mice (background strain of FGF21-deficient mice) and augmented immobility behaviour in a forced swimming test after social defeat stress. On the other hand, overexpression of FGF21 by adeno-associated virus vectors did not significantly change behaviours either in wild-type male mice or FGF21-deficient male mice. The present data are consistent with the view that endogenous FGF21, possibly during the developmental period, has an inhibitory action on stress-induced depression-like behaviour in male rodents.
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Social contact reduces stress responses in social animals. Mice have been shown to show allogrooming behaviour toward distressed conspecifics. However, the precise neuronal mechanisms underlying allogrooming behaviour remain unclear. In the present study, we examined whether mice show allogrooming behaviour towards distressed conspecifics in a social defeat model and we also determined whether oxytocin receptor-expressing neurons were activated during allogrooming by examining the expression of c-Fos protein, a marker of neurone activation. Mice showed allogrooming behaviour toward socially defeated conspecifics. After allogrooming behaviour, the percentages of oxytocin receptor-expressing neurones expressing c-Fos protein were significantly increased in the anterior olfactory nucleus, cingulate cortex, insular cortex, lateral septum and medial amygdala of female mice, suggesting that oxytocin receptor-expressing neurones in these areas were activated during allogrooming behaviour toward distressed conspecifics. The duration of allogrooming was correlated with the percentages of oxytocin receptor-expressing neurones expressing c-Fos protein in the anterior olfactory nucleus, insular cortex, lateral septum and medial amygdala. In oxytocin receptor-deficient mice, allogrooming behaviour toward socially defeated cage mates was markedly reduced in female mice but not in male mice, indicating the importance of the oxytocin receptor for allogrooming behaviour in female mice toward distressed conspecifics. The results suggest that the oxytocin receptor, possibly in the anterior olfactory nucleus, insular cortex, lateral septum and/or medial amygdala, facilitates allogrooming behaviour toward socially distressed familiar conspecifics in female mice.
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Gentle touch contributes to affiliative interactions. We investigated the effects of gentle stroking in female rats on the development of affiliative behaviors toward humans and we exploratively examined brain regions in which activity was influenced by stroking. Rats that had received stroking stimuli repeatedly after weaning emitted 50-kHz calls, an index of positive emotion, and showed affiliative behaviors toward the experimenter. Hypothalamic paraventricular oxytocin neurons were activated in the rats after stroking. The septohypothalamic nucleus (SHy) in the post-weaningly stroked rats showed decreased activity in response to stroking stimuli compared with that in the non-stroked control group. There were negative correlations of neural activity in hypothalamic regions including the SHy with the number of 50-kHz calls. These findings revealed that post-weaning stroking induces an affiliative relationship between female rats and humans, possibly via activation of oxytocin neurons and suppression of the activity of hypothalamic neurons.
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Conducta Animal/fisiología , Encéfalo/fisiología , Hipotálamo/fisiología , Percepción del Tacto/fisiología , Animales , Mapeo Encefálico , Femenino , Humanos , Neuronas/metabolismo , Neuronas/fisiología , Oxitocina/metabolismo , Estimulación Física , Ratas , DesteteRESUMEN
Multiple sequential actions, performed during parental behaviors, are essential elements of reproduction in mammalian species. We showed that neurons expressing melanin concentrating hormone (MCH) in the lateral hypothalamic area (LHA) are more active in rodents of both sexes when exhibiting parental nursing behavior. Genetic ablation of the LHA-MCH neurons impaired maternal nursing. The post-birth survival rate was lower in pups born to female mice with congenitally ablated MCH neurons under control of tet-off system, exhibiting reduced crouching behavior. Virgin female and male mice with ablated MCH neurons were less interested in pups and maternal care. Chemogenetic and optogenetic stimulation of LHA-MCH neurons induced parental nursing in virgin female and male mice. LHA-MCH GABAergic neurons project fibres to the paraventricular hypothalamic nucleus (PVN) neurons. Optogenetic stimulation of PVN induces nursing crouching behavior along with increasing plasma oxytocin levels. The hypothalamic MCH neural relays play important functional roles in parental nursing behavior in female and male mice.
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Conducta Animal , Neuronas GABAérgicas/metabolismo , Hormonas Hipotalámicas/metabolismo , Melaninas/metabolismo , Oxitocina/metabolismo , Núcleo Hipotalámico Paraventricular/metabolismo , Hormonas Hipofisarias/metabolismo , Animales , Femenino , Hormonas Hipotalámicas/genética , Masculino , Melaninas/genética , Ratones , Ratones Transgénicos , Oxitocina/genética , Hormonas Hipofisarias/genéticaRESUMEN
The biological and psychological significance of oxytocin is increasingly recognized; however, reliable assays of oxytocin in biological samples have not been developed. We raised a new oxytocin polyclonal rabbit antibody against synthetic oxytocin. The affinity of antibodies to oxytocin was examined by a radio-immunoassay and compared with that of a previously validated antibody. One antibody showed affinity for oxytocin in the radio-immunoassay. We developed a solid-phase ELISA for oxytocin using this antibody and compared it with existing methods. The newly developed ELISA showed comparable results using urine samples but not using serum samples. These results indicate that the new ELISA is useful for urinary oxytocin; further modifications, such as different extraction methods, are needed for its application to serum oxytocin.
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Anticuerpos , Oxitocina , Animales , Ensayo de Inmunoadsorción Enzimática/veterinaria , Inmunoensayo/veterinaria , ConejosRESUMEN
Oxytocin has been revealed to work for anxiety suppression and anti-stress as well as for psychosocial behavior and reproductive functions. Oxytocin neurons are activated by various stressful stimuli. The oxytocin receptor is widely distributed within the brain, and oxytocin that is released or diffused affects behavioral and neuroendocrine stress responses. On the other hand, there has been an increasing number of reports on the role of oxytocin in allostasis and resilience. It has been shown that oxytocin maintains homeostasis, shifts the set point for adaptation to a changing environment (allostasis) and contributes to recovery from the shifted set point by inducing active coping responses to stressful stimuli (resilience). Recent studies have suggested that oxytocin is also involved in stress-related disorders, and it has been shown in clinical trials that oxytocin provides therapeutic benefits for patients diagnosed with stress-related disorders. This review includes the latest information on the role of oxytocin in stress responses and adaptation.